The primary mechanisms involved in renal hypertension are activation of the reninangiotensin system, stimulation of the sympathetic nervous system and elevation of cardiac output due to volume expansion. There are data to suggest that the predominance of one of these mechanisms during hypertension may be related to the sodium balance and water balance of the animal. The periventricular tissue of the anteroventral third ventricle region of the hypothalamus (AV3V) is necessary for sodium and water regulation and for the development of 1-K, 1-W Grollman and 2-K, 1-C Goldblatt models of hypertension. The objectives of this study are threefold. First, the role of angiotensin, increased sympathetic tone and elevated cardiac output will be assessed at 3, 14 and 28 days after surgery in these hypertensive models. Second, the ability of lesions of the AV3V to interfere with these mechanisms will be determined. Third, the function of sodium and water balance in determining the role of these mechanisms will be ascertained by manipulating the sodium and fluid intake of the animal. During the two phases of this study, all experiments will be performed in conscious rats that are free to move about in their cage. For each phase, AV3V lesioned and sham lesioned rats will be subjected to various dietary and hydrational regimens to independently alter the sodium and water status of the animal. The animals will then be subjected to hypertensive or sham hypertensive surgery. In the first part of the study, cardiac output, metabolic balance data and plasma and extracellular fluid volume measurements will be determined throughout the hypertensive process to assess the role of volume factors. The second part of the study will ascertain the involvement of the renin-angiotensin system and sympathetic nervous system. A pulsed Doppler flowmeter system will be used to assess changes in regional vascular resistance during pharmacological blockade of angiotensin receptors and autonomic ganglia. These studies will provide an understanding of the role of sodium and water balance in determining the mechanisms contributing to hypertensive disease.